Implantable superhydrophobic surfaces

ABSTRACT

Bio-adhesive textured surfaces are described which allow implants to be localized within a living body. Hierarchical levels of texture on an implantable medical device, some capable of establishing a Wenzel state and others a Cassie state, may be employed to interface with living structures to provide resistance to device migration. Since a gaseous state is traditionally required to establish a Cassie or Wenzel state, and gases do not remain long in living tissue, described herein are tissue/device interactions analogous to the above states with the component normally represented by a gas replaced by a bodily constituent, wherein separation of tissue constituents develops and an analogous Cassie, Wenzel, or Cassie-Wenzel state evolves. Further methods of making molds to produce said devices are described herein.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/368,531 filed Mar. 28, 2019, which is a continuation of U.S. patentapplication Ser. No. 13/745,381, now U.S. Pat. No. 10,292,806, filedJan. 18, 2013, which claims the benefit of priority to U.S. ProvisionalApplication No. 61/589,907, filed on Jan. 11, 2013, the contents ofwhich are hereby incorporated by reference in their entirety.

TECHNICAL FIELD

The present disclosure provides implantable medical devices comprisingsurface textures on a substrate that, upon implantation in a hosttissue, create interfaces with liquids present in the host tissue. Theimplants in certain embodiments advantageously prevent or reduce devicemigration after implantation into the body.

BACKGROUND

The Cassie and Wenzel phenomena occur classically when three phases arein contact with one another. For example, one can have one solid and twoliquid phases in contact, with the two liquid phases being different intheir hydrophobicity. In the body, the respective states lead to theformation and retention on an implant of a liquid hydrophilic film inthe Cassie state and retention of tissue (containing lipids) in theWenzel state. These are clinically useful attributes for localizing animplant within living tissue.

Shear is motion of an implant parallel to a tissue surface, and peel ismotion of an implant perpendicular to a tissue surface. Clinically, animplant with high shear force resists migration in the body and animplant with low peel force can be repositioned easily by the clinicianduring the surgical procedure.

The interaction of a solid textured surface with water in a gaseousenvironment is described by the Cassie-Baxter model. In this model, airis trapped in the microgrooves of a textured surface and water dropletsrest on a compound surface comprising air and the tops ofmicro-protrusions. The importance of a fractal dimension betweenmultiple scales of texture is well recognized and many approaches havebeen based on the fractal contribution, i.e., the dimensionalrelationship between different scales of texture. However, regardless ofthe material (organic or inorganic) used and geometric structure of thesurface texture (particles, rod arrays, or pores), multiple scales oftexture in combination with low surface energy has been required toobtain the so called super hydrophobic surfaces.

Super hydrophobicity is variously reported as a material exhibiting acontact angle with water that is greater than the contact anglesachievable with smooth but strongly hydrophobic materials. The consensusfor the minimum contact angle for a super hydrophobic substance is 150degrees.

A hydrophobic surface repels water. The hydrophobicity of a surface canbe measured, for example, by determining the contact angle of a drop ofwater on a surface. The contact angle can be measured in a static stateor in a dynamic state. A dynamic contact angle measurement can includedetermining an advancing contact angle or a receding contact angle withrespect to an adherent species such as a water drop. A hydrophobicsurface having a large difference between advancing and receding contactangles (i.e., high contact angle hysteresis) presents clinicallydesirable properties. Water or wet tissue can travel over a surfacehaving low contact angle hysteresis more readily than across a surfacehaving a high contact angle hysteresis, thus the magnitude of thecontact angle hysteresis can be equated with the amount of energy neededto move a substance across a surface in shear. In clinical applications,a high contact angle reduces the mobility of the implant in situ.

The classic motivation from nature for surface texture research is thelotus leaf, which is super hydrophobic due to a hierarchical structureof convex cell papillae and randomly oriented hydrophobic wax tubules,which have high contact angles and low contact angle hysteresis withwater and show strong self-cleaning properties. A lesser-knownmotivation from nature is the red rose petal, with a hierarchicalstructure of convex cell papillae ornamented with circumferentiallyarranged and axially directed ridges, which have a moderate contactangle and high contact angle hysteresis.

The contact angle is a measure of the amount of water directly incontact with the implant surface, while the contact angle hysteresis isan inverse measure of the degree to which water is mobile on a surface.The natural evolutionary motivation for each of these states is quitedistinct.

In the case of the lotus leaf, and botanical leaves generally, minimalcontact with water and high water mobility results in preferentialadherence of the water to particulate contaminants, which are clearedfrom the leave as the water runs off. This serves to reduce lightabsorbance by surface contaminants and increase photosyntheticefficiency.

In the case of the rose petal, and botanical petals generally as opposedto leaves, most pollinators are attracted to high tension water sourceswhich provide ready accessibility without drowning the insect.

Thus, high contact angle paired with high contact angle hysteresis ispreferred where the evolutionary stimulus is reproduction in botanicals,and high contact angle paired with low contact angle hysteresis ispreferred where the evolutionary stimulus is metabolism and growth.

Considering for a moment a single texture scale, when water is placed ona textured surface it can either sit on the peaks of the texture or wickinto the valleys. The former is called the Cassie state, and the laterthe Wenzel state. When the Wenzel state is dominant, both the contactangle and contact angle hysteresis increase as the surface roughnessincreases. When a roughness factor exceeds a critical level, however,the contact angle continues to increase while the hysteresis startsdecreasing. At this point, the dominant wetting behavior changes, due toan increase in the amount of air trapped at the interface between thesurface and water droplet. In the present context, the gaseous state isreplaced with a hydrophobic state; for example, a lipid. The hydrophobicstate may be a liquid or a solid derived from the host tissue.

In mixed Wenzel-Cassie states it is possible to have high contact angleand high contact angle hysteresis. However, texture alone is only oneaspect, the hydrophobicity of a textured solid relative to theinteracting environment is also important.

Water possesses a dipole structure which makes it attractive to anyother substance that is charged. Implantable molecules with a chargesurplus localized at a specific location on the molecule renders thatmolecule hydrophilic. In the case of polymers, the charges canassociate, and the bulk substance can possess a macroscopic surfacecharge. And in such macroscopic assemblages, these materials arestrongly water attractive. And when those macroscopic charge localitiesare associated with surface texture, then the implant material becomessuper hydrophilic.

Thus, while it is generally advantageous for an implant to behydrophilic, and associate readily with water in living tissue, thisassociation creates a fluid surface between the implant and the tissue,which acts as a lubricant. Generally, it is disadvantageous for animplant to move from a position determined by a clinician, and generallyit is disadvantageous for an implant to require suture or other physicalmeans of localization. Therefore, utilization of an in situ analog tothe Cassie-Wenzel state to localize an implant in living tissue isclinically desirable.

BRIEF SUMMARY

It is to be understood that both the foregoing general description andthe following detailed description present embodiments of the disclosureand are intended to provide an overview or framework for understandingthe nature and character of the disclosure as it is claimed. Thedescription serves to explain the principles and operations of theclaimed subject matter. Other and further features and advantages of thepresent disclosure will be readily apparent to those skilled in the artupon a reading of the following disclosure.

The present disclosure provides an implantable medical device comprisingat least two surface textures on a substrate, wherein upon implantationin a host tissue, the surface textures form interfaces with liquidspresent in the host tissue, wherein a part of the surface texturecontacts lipids present in the host tissue to form a first interface; apart of the surface texture contacts water present in the host tissue toform a second interface; and a part of the surface texture traps airbetween the device and the host tissue; wherein the resulting interfaceshave a contact hysteresis angle of at least 5 degrees.

The methods and embodiments of the disclosure are applicable toabsorbable and permanent implantable materials, where absorbablematerials are preferred. The disclosure relates to physiologicallyabsorbable, non-fibrogenic, hydrophilic materials that are maderelatively hydrophobic during a first time interval by the addition ofsurface texture. Alternatively, the disclosure relates tophysiologically absorbable, generally fibrogenic, hydrophobic materialsthat are made relatively hydrophilic during a first interval by theaddition of surface texture. These surface textures are employed tolocalize these implants within a living body.

The disclosure relates to implantable, absorbable sheets which arehydrophilic, and possibly swell or even dissolve in situ, whereby theaddition of a surface texture increases the force threshold fordislocation of a device after implantation.

Furthermore, the disclosure relates to implantable sheets with one sidewith an enhancement as described with respect to a first particularpurpose and a second side with an enhancement as described with respectto a second particular purpose.

The disclosure relates to implantable devices with surface texturespossessing an affinity for tissue, which allows them to be pealed from atissue surface and repositioned peri-operatively but resists sliding andfolding after implantation.

One object of the present disclosure is to provide implantable medicaldevices comprising surface textures that initially create classicalCassie and Wenzel states when exposed to an aqueous environment in amammalian body. Furthermore, implantable medical devices disclosedherein may form analogs to Wenzel and Cassie states after a period oftime in the host tissue that involve a solid hydrophilic phase, a liquidhydrophobic phase, and a liquid hydrophilic phase. In these modifiedWenzel and Cassie states, the trapped phase analogous to the classicalgaseous phase is the host derived hydrophobic phase.

Further provided herein are implantable medical devices comprisingtextures that after a period of time after implantation replace agaseous phase with a solid hydrophobic phase. Implantable, absorbablesheets comprised of a hydrophilic substrate that can swell or evendissolve in situ, whereby the addition of a hydrophobic surface texturereduces the rate of absorption or conformal change in situ.

For example, implantable, absorbable sheets comprising a hydrophilicsubstrate are provided, that can possibly swell or even dissolve insitu, whereby the addition of a hydrophobic surface increases the forcerequired to translate, rotate, fold, or shrink the area of an implant.

Further provided herein are implantable medical devices, wherein thedominance of the Wenzel state over the Cassie state, or the converse, ortheir analogues, can evolve as a function of time as the outer surfacesof the device are removed by hydrolysis or enzymatic degradation.

Further provided herein are implantable medical devices, whereinaccentuation of surface charge and surface energy occurs whereby suchthat water is always in association with the implant surface, eventhough any particular water molecule may have a short residence time onthe implant surface.

In further embodiments, implantable medical devices are provided,wherein tissue interaction of the implant surface results in tissueassociation with the implant surface, and in particular implantassociation with a lipid constituent of the tissue.

In particular, the disclosure describes a surface super hydrophobiceffect wherein resistance to implant sliding, rolling, folding or otherconformal changes of an implantable medical device is resisted.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A-B. General view of an implantable prosthetic of the presentdisclosure possessing a hierarchical surface.

FIG. 2A. Schematic of maximum communication structure C=1.

FIG. 2B. Schematic of communication structure C=0.25.

FIG. 2C. Schematic of minimum communication structure C→0.

FIG. 3A-B. A method of manufacture of an implantable prosthetic of thepresent disclosure.

FIG. 4. Example of Sierpinski gasket surface texture.

FIG. 5. Example of Apollonian gasket surface texture.

FIG. 6. Example of a petal-mimic surface texture.

FIG. 7A-7D. Examples of Kock snowflake surface texture.

FIG. 8. Example of an implantable with at least one side immediatelytissue adhesive.

FIG. 9. Example of an implantable where the surface texture makes theimplant hydrophobic to reduce the rate of absorption.

FIG. 10. Example of an implantable where the surface texture makes theimplant hydrophilic.

FIG. 11. Example of an implantable where the surface texture makes theimplant hydrophilic to increase the rate of absorption.

DETAILED DESCRIPTION

Reference now will be made in detail to the embodiments of the presentdisclosure, one or more examples of which are set forth herein below.Each example is provided by way of explanation of the embodiments of thepresent disclosure and is not a limitation. In fact, it will be apparentto those skilled in the art that various modifications and variationscan be made to the teachings of the present disclosure without departingfrom the scope or spirit of the disclosure. For instance, featuresillustrated or described as part of one embodiment, can be used withanother embodiment to yield a still further embodiment.

Thus, it is intended that the present disclosure covers suchmodifications and variations as come within the scope of the appendedclaims and their equivalents. Other objects, features and aspects of thepresent disclosure are disclosed in or are obvious from the followingdetailed description. It is to be understood by one of ordinary skill inthe art that the present discussion is a description of exemplaryembodiments only and is not intended as limiting the broader aspects ofthe present disclosure.

One embodiment provides an implantable medical device comprising atleast two surface textures on a substrate, wherein upon implantation ina host tissue, the surface textures form interfaces with liquids presentin the host tissue, wherein a part of the surface texture contactslipids present in the host tissue to form a first interface; a part ofthe surface texture contacts water present in the host tissue to form asecond interface; and a part of the surface texture traps air betweenthe device and the host tissue; wherein the interfaces have a contacthysteresis angle of at least 5 degrees.

The medical devices may comprise the surface texture material, or themedical devices may comprise other materials commonly used in the arthaving the surface texture material disposed thereon. The surfacetexture refers to a microscale texture or pattern disposed in thesubstrate material, for example, as described by the methods describedherein below. In particular embodiments, the surface texture comprises ahierarchical structure.

In particular embodiments, the contact hysteresis angle ranges from atleast 5 degrees to about 90 degrees. In other embodiments, the contacthysteresis angle ranges from at least 5 degrees to about 75 degrees,while in further embodiments, the contact angle hysteresis ranges fromabout 10 degrees to about 75 degrees.

In another embodiment, after a period of time after implantation,trapped air is replaced by lipids derived from the host tissue.Furthermore, in some embodiments, after a period of time, the interfacescomprise: a) a solid hydrophilic phase, b) a liquid hydrophobic phase,and c) a liquid hydrophilic phase. In yet another embodiment, theimplantable medical device of claim 1, wherein the trapped air isreplaced by a liquid hydrophobic phase after a period of time. In otherembodiments, after a period of time, the trapped air is replaced by ahydrophobic material derived from host tissue. For example, the periodof time may be about 5 minutes to 12 hours, or more particularly, about5 minutes to about 6 hours, or about 30 minutes to about 6 hours.

The implantable medical devices provided herein advantageously resistmigration in the body after implantation. For example, in someembodiments, the shear force to translate the device relative to hosttissue exceeds about 50 grams per square centimeter. In certainembodiments, the shear force may range from about 50 to about 200 gramsper square centimeter, about 50 to about 150 grams per squarecentimeter, or about 70 to about 150 grams per square centimeter.

In another embodiment, the surface textures comprise hydrophilicabsorbable materials, wherein the hydrophilic absorbable materials aremade less hydrophilic by the surface textures, and the surface texturesreduce the rate of absorption or conformal change of the medical devicein the host tissue. In other embodiments, the surface textures comprisehydrophobic absorbable materials, wherein the hydrophobic absorbablematerials are made less hydrophobic by the surface textures, and thesurface textures increase a rate of absorption or conformal change ofthe medical device in the host tissue.

In other embodiments, at least one surface texture comprises absorbablematerials, wherein the at least one surface texture is modified byabsorption, such that the at least one surface texture becomes morewetting or less wetting as the medical device is absorbed.

In certain embodiments, wherein the surface textures have a rate ofabsorbance in the host tissue that mitigates tissue adhesion and implantmigration in a first time interval and becomes smooth, hydrophilic,rapidly absorbing and non-fibrogenic material in a second time interval.For example, a first time interval may range from about 5 minutes toabout 6 hours, or about 10 minutes to about 6 hours, about 10 minutes toabout 3 hours, or about 10 minutes to about 30 minutes, and a secondtime interval may range from about 30 minutes to about 12 hours, about30 minutes to about 6 hours, about 1 hour to about 6 hours or about 3hour to about 6 hours.

In certain embodiments, at least one surface texture comprises a smallerpitch of 10 nanometers to 1 micron, and another surface texturecomprises a pitch of 2 microns to 100 microns, wherein the smallersurface texture is disposed on the larger surface texture, such that ahierarchical structure is provided. In some embodiments, the smallersurface textures trap the air, while the larger surface texture does nottrap air. In a different embodiment, the larger surface texture trapsair and the smaller surface texture does not trap air. The interfacesthus formed depend in part on the pitch size, the pattern of thetexture, and/or the substrate material used to prepare the surfacetexture, as described in more detail hereinbelow. In a particularembodiment, the first interface excludes attachment of a first hostderived substance and the second interface promotes attachment of asecond host derived substance. For example, the first host derivedsubstance may be a microbe and the second host derived substance may behost cells. In another example, the first host derived substance is aprotein and the second tissue derived substance is host tissue. Incertain embodiments, the first host derived substance is hydrophobic forone texture and the second host derived substance is hydrophobic for adifferent texture. In other embodiments, the first host derivedsubstance is a protein and the second host derived substance is hosttissue.

In further embodiments, upon implantation in the host tissue, a surfacecharge of at least one surface texture increases such that water is morestrongly bonded to the substrate surface, but not so strongly bonded soas to preclude exchange of water molecules bonded to said substratesurface with surrounding water in the host tissue. For example, a layerof water may adhere to the surface of the device and said water layerreduces the rate of protein molecule adsorption to said texturedsurface, relative to a device comprised of said substrate withoutsurface texture. Furthermore, a layer of water may adhere to the surfacetextures of the device, such that the water layer reduces a rate ofprotein molecule adsorption to the textured surface, relative to adevice without the surface textures.

In particular embodiments, the substrate may be porous. For example, thesubstrate may comprise three-dimensionally interconnected pores.

In some embodiments, the first surface texture forms a Cassie state whenimplanted in host tissue and the second surface texture forms a Wenzelstate when implanted in host tissue. In further embodiments, at leastone of the surface textures comprises fibers embedded in and protrudingfrom the substrate, and the fibers are bifurcated at least once on atleast one spatial scale different from a pitch of other surface texturesof the device. In yet another embodiment, at least one of said surfacetextures is comprised of fibers embedded at both ends in said substrateand said fiber and protrude from said substrate and said fibers formloops with at least one diameter different from the pitch of othersurface textures of the medical device.

In certain embodiments, the surface textures may comprise or be similarto certain mathematical fractal shapes. For example, in someembodiments, at least one surface texture comprises a Koch snowflakepattern, a Sierpinski gasket pattern, Apollonian gasket pattern, or adiffusion limited aggregation pattern.

In certain embodiments, the aforementioned implantable medical devicescomprise two sides, such as a sheet structure, wherein the two sideshave different surface texture patterns. In one embodiment, the surfacetextures form interfaces with liquids present in host tissue, wherein atleast one surface texture traps air between the device and tissue and atleast one other surface texture does not trap air between the device andtissue, and wherein the resulting interfaces generate a contacthysteresis angle of at least 5 degrees on one side (for example, thecontact angle hysteresis can be at least 5 degrees to about 90 degrees,at least 5 degrees to about 75 degrees, or about 10 degrees to about 75degrees), and less than 5 degrees (for example, an angle of about 0.1 toless than 5 degrees, or more particular, about 0.5 to less than 5degrees, or more particularly, about 0.5 to about 3 degrees) on theother side of the device.

It should be understood that the structures of the present disclosureare not intended to be strictly superhydrophobic and should not belimited on that basis. For example, a typically hydrophilic material canbe rendered more hydrophobic by the addition of surface structure, butsuch addition does not require the surface to be superhydrophobic, bythe usual definitions.

While not being bound by any particular theory, the implantable medicaldevices can be further understood as explained by the principlesdescribed below. A scale of interaction is defined by the spatialdimensions of a surface texture of an implantable device. In certainembodiments, the surface texture hierarchical, meaning one texture of agiven dimension is applied upon a second texture of larger dimension. Ahierarchical design is characterized by at least two spatial scales. Onescale is typically on the order of 10's of micrometers (microns) andanother on the order 100's of nanometers up to a few microns. Thesurface texture may induce one state with a large difference betweenpreceding and receding contact angles (contact angle hysteresis), oralternatively another state with a small contact angle hysteresis.States of interest, and there in situ analogues, are known respectivelyas Wenzel and Cassie states. Each of the hierarchical spatial scales mayinduce separately a Wenzel or Cassie state, such that combinations arepossible on a multiplicity of spatial scales.

These states are typically characterized by three phase contacts, andclassically consist of solid, liquid, and gaseous phases. These phasecontacts are initiated by the dimensionality of the surface texture.Since the gaseous component eventually dissipates in vivo by acombination of liquid evaporation into the gaseous domain and gasdissolution into the liquid domain, the Cassie state could eventuallyevolve into the Wenzel state in living tissue.

The present disclosure relates to implantable materials comprised oftextures that initially create Cassie and Wenzel states when exposed toan aqueous environment in a mammalian body. These states evolve in situ,and their evolution analogues differ from typical Wenzel and Cassiestates in that they involve a solid hydrophilic phase, a liquidhydrophobic phase, and a liquid hydrophilic phase or a solid hydrophobicphase, a liquid hydrophilic phase, and a liquid hydrophobic phase. Inthese modified Wenzel and Cassie states, the trapped phase analogous tothe classical gaseous phase is the liquid hydrophobic phase.Alternatively, a trapped gaseous phase is preferentially replaced by aliquid hydrophilic phase. In this alternative construction, at least oneof the other phases is hydrophobic.

The Cassie and Wenzel phenomena, occur classically when three phases arein contact with one another. For example, one can have one solid and twoliquid phases in contact, with the two liquid phases being different intheir hydrophobicity. In the body, the respective states lead to theformation and retention on an implant of a liquid hydrophilic film inthe Cassie state and retention of tissue (containing lipids) in theWenzel state. These are clinically useful attributes for localizing animplant within living tissue.

In the Cassie state the implant is resistant to cellular adhesion. Inthe Wenzel state the implant is reversibly adherent to tissue. In hybridCassie-Wenzel states, where one texture scale is Wenzel and the other isCassie, the implant can be both localizing in shear to a tissue surfaceand releasable in peal. Shear is motion of an implant parallel to atissue surface, and peal is motion of an implant perpendicular to atissue surface. Clinically, an implant with high shear force resistsmigration in the body and an implant with low peal force can berepositioned easily by the clinician during the surgical procedure.

Opposite sides of an implant may be biased toward tissue localization onone side and resistant to tissue adhesion on the other side, while bothsides may exhibit both properties to greater or lesser extent. Thedominance of Wenzel over Cassie, or the converse, can evolve as afunction of time as the outer surfaces of the implant are removed byhydrolysis or enzymatic degradation. In particular cases, the spatialfrequency of the various structure scales may be modulated within theimplant, such that as the implant dissolves it presents a changingspatial frequency as the surface layers of the implant are removed.

Alternatively, the surface texture may be chosen such that one side hashigh surface area relative to a second side with low surface area.

Alternatively, the surface texture may be chosen to modulate thehydrophobicity of a single implant material to control water absorbance,biodegradation, and drug elution differentially relative to regions orwhole sides of the implant.

The interaction of a solid textured surface with water in a gaseousenvironment is described by the Cassie-Baxter model. In this model, airis trapped in the microgrooves of a textured surface and water dropletsrest on a compound surface comprising air and the tops ofmicro-protrusions. The importance of a fractal dimension betweenmultiple scales of texture is well recognized and many approaches havebeen based on the fractal contribution, i.e., the dimensionalrelationship between different scales of texture. However, regardless ofthe material (organic or inorganic) used and geometric structure of thesurface texture (particles, rod arrays, or pores), multiple scales oftexture in combination with low surface energy has been required toobtain the so called super hydrophobic surfaces.

Super hydrophobicity is variously reported as a material exhibiting acontact angle with water that is greater than the contact anglesachievable with smooth but strongly hydrophobic materials. The consensusfor the minimum contact angle for a super hydrophobic substance is 150degrees, so in this context most of the embodiments of the presentdisclosure are not strictly super hydrophobic because our end state isnot a classical gas entrapping state, but rather the gas is replaced bya hydrophobic phase.

A hydrophobic surface repels water. The hydrophobicity of a surface canbe measured, for example, by determining the contact angle of a drop ofwater on a surface. The contact angle can be measured in a static stateor in a dynamic state. A dynamic contact angle measurement can includedetermining an advancing contact angle or a receding contact angle withrespect to an adherent species such as a water drop. A hydrophobicsurface having a large difference between advancing and receding contactangles (i.e., high contact angle hysteresis) presents clinicallydesirable properties. Water or wet tissue can travel over a surfacehaving low contact angle hysteresis more readily than across a surfacehaving a high contact angle hysteresis, thus the magnitude of thecontact angle hysteresis can be equated with the amount of energy neededto move a substance across a surface in shear. In vivo, a high contactangle reduces the mobility of the implant in situ.

One motivation for surface texture research is the lotus leaf, which issuper hydrophobic due to a hierarchical structure of convex cellpapillae and randomly oriented hydrophobic wax tubules, which have highcontact angles and low contact angle hysteresis with water and showstrong self-cleaning properties. An explored structure is the red rosepetal, with a hierarchical structure of convex cell papillae ornamentedwith circumferentially arranged and axially directed ridges, which havea moderate contact angle and high contact angle hysteresis.

Considering for a moment a single texture scale, when water is placed ona textured surface it can either sit on the peaks of the texture or wickinto the valleys. The former is called the Cassie state, and the laterthe Wenzel state. When the Wenzel state is dominant, both the contactangle and contact angle hysteresis increase as the surface roughnessincreases. When a roughness factor exceeds a critical level, however,the contact angle continues to increase while the hysteresis startsdecreasing. At this point, the dominant wetting behavior changes, due toan increase in the amount of air trapped at the interface between thesurface and water droplet. In the present context, the gaseous state isreplaced with a hydrophobic state; for example, a lipid. The hydrophobicstate may be a liquid or a solid derived from the host tissue. In mixedWenzel-Cassie states it is possible to have high contact angle and highcontact angle hysteresis.

Water possesses a dipole structure which makes it attractive to anyother substance that is charged. Implantable molecules with a chargesurplus localized at a specific location on the molecule renders thatmolecule hydrophilic. In the case of polymers, the charges canassociate, and the bulk substance can possess a macroscopic surfacecharge. And in such macroscopic assemblages, these materials arestrongly water attractive. And when those macroscopic charge localitiesare associated with surface texture, then the implant material becomessuper hydrophilic.

The term super hydrophilic has various meanings in the literature, andin many cases simply refers to the rendering of a substance morehydrophilic, or a decrease in contact angle relative to a flat surfaceof the same substance. Here, it is meant the accentuation of surfacecharge and surface energy such that water is always bonded to thesubstrate surface, even though any particular water molecule may have ashort residence time on the implant surface.

It should be understood that none of the structures of the presentdisclosure are intended to be strictly super hydrophobic in theclassical sense when implanted and should not be limited on that basis.For example, a typically hydrophilic material can be rendered morehydrophobic by the addition of surface structure, but such addition doesnot require the surface to be super hydrophobic, by the usualdefinitions. In particular, a super hydrophobic surface in contact withliquid in open air is not super hydrophobic when implanted in a wetenvironment such as living tissue. Thus, while the present disclosuresare super hydrophobic outside the body, they are not super hydrophobicwhen implanted.

A surface is defined as super hydrophobic when the water contact angleis greater than 150 degrees in open air. The highest contact angle for awater droplet on a smooth surface is dictated by the electronicstructure of the molecules comprising the smooth surface and isapproximately 120 degrees. For example, CF₃ groups have a low surfaceenergy of 6.7 mJ/m².

Beyond a contact angle of 120 degrees, the fine surface roughnessbecomes the dominant factor in increasing the contact angle. Themechanisms responsible for the effect of surface roughness wereaddressed by Wenzel and later by Cassie and Baxter. Thus, a superhydrophobic surface must possess a surface roughness. It is possible torender hydrophilic substances hydrophobic by use of texture. Thefollowing are original derivations of contact angles and designprinciples for implant environments, and thus are not generally know,and constitute teaching of the present disclosure.

The interaction of water with a smooth surface is characterized byYoung's angle θy, and the wettability is quantified by the Youngequation,

cos θy=(γs-g−γl-s)/γl-g,

where γs-g, γl-s, and γl-g represent the interfacial tensions ofsolid-gas, s-g, liquid-solid l-s, and liquid-gas, l-g interfaces,respectively.

For a textured surface, there are two water contact states correspondingfirst to water filling the interstitial sites (Wenzel) and second gastrapped in the interstitial sites by a layer of water (Cassie). Fortextured surfaces with a multiplicity of surface texture spatial scalesit is possible for the larger scaled texture to form contact with waterin the Wenzel state and for smaller scale texture to form contact withwater in the Cassie state. This mixed water contact state is commonlycalled the Cassie wettable state, or the Cassie-Wenzel state.

A characterization of the Wenzel state can be obtained by generalizingthe Young equation as follows:

cos θa,w=r cos θy,

where r is termed the “roughness factor” and defined as the ratio of theactual area of contact on a rough surface to the projected area ofcontact in the contact plane

A characterization of the Cassie state can be obtained by generalizingthe Young equation as follows

cos θa,c=r f cos θy+f−1,

where f represents the fraction of the projected area that is wetted bythe liquid. These equations relate surface energy to the geometry ofsolid/liquid interface in equilibrium. In the implant environment,nothing is static, and the Brownian motion of different chemicalconstituents is responsible for repeated association and disassociationwith a surface. The surface may itself be changing where a portion orall of a surface is absorbable.

When the energy to form a liquid/solid interface is different from theenergy to remove a liquid/solid interface, then their contact angles aredifferent, and this difference is called contact angle hysteresis.Contact angle hysteresis is defined here as the difference betweenassociation and disassociation contact angles. This hysteresis occursdue to the wide range of “metastable” states which can be observed asthe liquid surface tension interacts with the surface of a solid at thephase interface.

The adhesive aspect of the “petal effect”, a Cassie wettable state, isone in which the energy to associate a liquid with a surface is lessthan the energy required to disassociate that interface, even in caseswhere the overall surface energy is quite low (high contact angle). Thecontact angle hysteresis is achieved by allowing one scale of roughnessto be Wenzel and another scale of roughness to be Cassie. When allscales of roughness are Cassie (non-wetting), then formation of aliquid/solid interface requires relatively more energy than for theCassie wettable state, and the association of liquid/solid contact andthe disassociation of liquid/solid contact are approximately equallydisfavored (low contact angle hysteresis). This results in the “lotuseffect” where liquid/solid interface comprises low surface area and iseasily disassociated.

Thus, the lotus (Cassie) and petal (Cassie wettable) effects can becharacterized by the following equation:

cos θa=Q1 cos θ1±Q2 cos θ2

which describes the effect of surface heterogeneity on the contactangle. In this equation, θa, the apparent angle, is the weighted averageof the contact angles of two roughness scales on the surface. Thisequation can be generalized to any number of scale hierarchies. Thequantities Q1 and Q2 represent the fraction of the surface covered byliquid/solid interface for each of the roughness scales characterized bycontact angles θ1 and θ2. When θ1-θ2 is large (contact anglehysteresis), θa characterizes a petal effect and is generally adhesive.When θ1-θ2 is small, θa characterizes a lotus effect and is generallyrepulsive.

Thus, for the petal state one of the θ is θac (Cassie) and the other θis θaw (Wenzel) and for the lotus state both of the θ are θac (Cassie).For example, setting θ1=θac and θ2=θaw, then the complete equation is

cos θa=Q1 cos θac±Q2 cos θaw=Q1(rf cos qy+f−1)±Ω2(r cos qy)

Note that the contact angle is determined by both a) thehydrophobicity/hydrophilicity (surface electronic structure) of thesubstance comprising the surface and b) its texture. The above equationassumes the solid surface is comprised of a single substance andrepresents only the hierarchical structure of the surface texture.

Now consider a solid surface with both hierarchical surface texture andhierarchical changes in surface hydrophobicity. Thus, the apparent angleθac or θaw is a function of both structure scale and surface electronicstructure. Thus, spatial structure and electronic structure areinterchangeable when

θac (spatial)=θac (electronic)

θaw (spatial)=θaw (electronic)

θa (spatial) is dependent solely on the Young equation, accordingly themost general equation for the apparent contact angles is

cos θa=Σ _(i=1,n)[Q _(i)(r _(i) fi cos θy _(i) +f _(i)−1)]±Σ_(i=n+1,m) Q_(i)(r _(i) cos θy _(i)).

In the implant environment the surface of a solid is modified byrelatively amphiphilic aqueous constituents residing in the body. Theimplant/tissue interfacial tension can be modified by amphiphilicconstituent addition caused by the adsorption of amphiphilic proteinsonto the implant and can be described by the Gibbs adsorption equation,which relates the surface excess concentration Γs to the interfacialtension γ by

Γs=−(1/k _(B) T)(dγ/d ln c _(p)).

Where c_(p) is the surface protein concentration, T is temperature andk_(B) is the Boltzmann constant.

When c_(p) exceeds a critical density the protein monolayer of l-g orl-s interface becomes saturated, because both γl-g and γl-s areunchanged. In vivo constituents are unable to reduce γl-s further tosatisfy the condition, γl-s<γs-g, at saturation and thus the surfaceremains in a hydrophobic range. Since the l-s interface is saturatedbefore the l-g interface is, contact angle reduction for in vivoconstituents is controlled by surface tension (γl-g). Contact anglehysteresis is generally increased with the surface proteinconcentration. Nonetheless, like the associated contact angle, contactangle hysteresis evolves to be independent of surface proteinconcentration as c_(p) approaches the critical protein density.

The above equations provide the means to design an implant with asurface which stays adhesive in the shear direction after implantation.

The present disclosure is directed to adapting the super hydrophobiceffect and related petal and lotus effects and in particular wettableCassie and pure Cassie states to an implant environment. Therefore,except where polymers are used which actively entrap a gas state on animplant surface (and those will be considered here), a gas state cannotbe relied upon to create the desired Cassie states. Biological fluidsare far from homogeneous, and are comprised of discrete hydrophilic andhydrophobic components, suspended macromolecules, and several sizescales of sub-cellular, cellular, and tissue structures.

The present application describes methods and devices which use Cassiestates that organize constituents of a liquid biologic medium to createan adhesive effect. These methods comprise the use of scale hierarchicalsurface geometry, scale hierarchical regions of surfacehydrophobicity/hydrophilicity, and scale hierarchical regions ofhydrophobic phase adhesion.

According to this disclosure, it is proposed to use spatiallyhierarchical surfaces as regards their geometry. In particular, surfacetextures that are linearly and fractally arranged in a scale rangingfrom tens of micrometers down to several nanometers. Considering thatonly the outermost portions of individual hierarchic levels are wetted(contact water), such structures should be characterized by a very smallsurface of effective contact between the solid and bodily aqueousfluids, preferably below 1% of the implant surface.

It should be understood that at any one scale, the percentage of waterassociation is critical, and not the absolute value of the amount ofwater association, such that at various fine scales the amount of waterinteraction with the surface may be very small or very large. Theclinical consequence could be great relative to the percentage of waterthat is interacting with the local surface structure, even if most ofthe surface is in contact with water. Conversely, in the non-contactarea and where air is initially trapped, lipid constituents arepreferentially attracted, particularly tissue constituents of lipophiliccharacter, which preferably replace the regions occupied by air.

In at least one embodiment of the present disclosure lipid filmsoriginating from the body attach to the implant, the result is that thefilm acts as a low energy surface which energetically disfavorstranslation of the implant parallel to the interfacial tissue surface.In particular, such films, some of which may be proteinaceous andhydrophobic, may undergo denaturation or polymerization, which acts as aglue to localize an implant.

In particular, an embodiment of the present disclosure is an implantedsurgical barrier, one side of one side of which possesses a Cassiewettable state for localizing the implant to tissue, and the other sidepossesses a pure Cassie state for resisting tissue adhesions.

In another embodiment, the substrate material may have on one side alayer which is relatively rapidly absorbable and hydrophilic and on theother side is a layer which is relatively slowly absorbed andhydrophobic such that the texture on the two sides produce a Cassiewettable state on one side and a super hydrophobic pure Cassie state onthe other side.

In another embodiment, the Cassie wettable state induces denaturation orpolymerization of aqueous dissolved proteins.

In another embodiment, the tissue adhesive surfaces of the presentdisclosure bind to tissue spontaneously in the presence of water.Without wishing to be bound by theory, it has been reported thathydrophobic bonding is based on very-long-range attractive forces. Theseforces are due to lipid separation resulting in a phase-like transitionin bodily fluid present at an implant site. This change is characterizedby a sudden, strong attractive force and by the formation of lipidbridges. In contradistinction, implantables with long-range attractiveforces are described.

In another embodiment of the present disclosure, such attractive forcesbetween a textured implant surface and tissue are employed to(reversibly) bind an implant to a surgical site.

In another embodiment, the surface texture of an implant may be chosento induce a filtering effect, wherein certain molecules, cellularstructures, or tissue components are attracted while others(particularly water) are repelled, and this attractive/repulsive effectvaries across different surface texture spatial scales. This screeningeffect permits a longer duration adhesive aspect by replacing initiallytrapped air with a lipid fraction. The lipid fraction may be connectivetissue rather than a liquid lipid fraction.

The present patent introduces the concept of using structured surfacesconsisting of non-communicating (closed cell) roughness elements toprevent the transition of trapped air to a hydrophilic fluidic mobilestate characterized by transition from the Cassie to the Wenzel state.The resistance to the Cassie to Wenzel transition can be furtherincreased by utilizing surfaces with nanostructured (instead ofmicrostructured) non-communicating elements, since the resistance isinversely related to the dimension of the roughness element.

One aspect of some embodiments of the present disclosure are dimpled orimpressed surfaces that offer increased resistance to droplet transitionto the Wenzel state compared to a dimensionally equivalent pillaredsurface. The presence of air trapped inside the non-communicatingcraters and the resistance to fluid motion offered by the craterboundaries and corners contribute to this increased resistance to thetransition to a Wenzel state and enhance adhesiveness in vivo.

The impressed or concave textured surfaces of the present disclosurepreferably possess a fractal structure or hierarchic structure, whereinthe first hierarchic level is located next to the coating substrate andeach successive level is located on the surface of forms of the previoushierarchic level and the shape of forms of higher hierarchic levelsreiterate the shapes of lower hierarchical levels and the structurecontains forms of at least two hierarchical levels.

The substrate of the biocompatible implants of the present disclosureare polymeric materials with possibly one or more nano-scale textures(up to 10 microns) with dimensional spacing of 10 to several thousandnanometers and at least one micro-scale texture with dimensional spacingof 10 to about 100 microns.

The polymeric material is preferably heat meltable without decompositionor alternatively soluble in a solvent, so that the texture may beembossed in the melt state or cast in the solvent state.

Generally, texture refers to topographical and porosity elements,including elevations and depressions on the surface and massdistribution in the volume of a polymeric surface and of the layercomprising the surface. The polymeric layers may be made of multiplepolymer types, and may contain other material being embedded in thepolymer and contributing to the topography, For example, non-polymericor polymeric fibers or particulate may be dispersed on the surface ofthe polymer substrate, these fibers may comprise more phases orcomponents. In particular, the fiber or particulate components maypossess absorption rates in a mammalian body slower than the bulkpolymer such that a desired texture is preserved for an extended periodduring the dissolution process. Alternatively, these slower absorbingelements are embedded in the polymeric substrate homogeneously or onseveral levels such that several different topologies are presentedduring the course of dissolution.

The textured implants of this disclosure can have many variants andcombinations that are specified as follows. For example, the implant canhave a homogenous bulk composition wherein grooves, ridges,protuberances or indentations are located, on at least two spatialscales, on the surface of implant. The implant can have a poroussubstrate with three dimensionally interconnected pores. The implant canhave a solid substrate with interconnected channels ornon-interconnected indentations on the implant surface. The implant canhave a first small scale texture embossed on a second larger scalestructure, or a hierarchical arrangement of such scales. The implant canhave a first small scale texture that is concave and non-communicatingembossed on a second larger scale structure that is convex andcommunicating, or a hierarchical arrangement of such structures. Theimplant can have a first small scale texture that is Cassie embossed ona second larger scale structure that is Wenzel, or the reverse. Theimplant can have grooves or ridges deployed in a step-like contour onlarger scale convex protuberances. The implant can have a semi-openstructure wherein hierarchical texture is located on cross elements,such that the semi-open structure itself comprises a texture. Theimplant can have fibers imbedded and protruding from the polymersubstrate, said fibers can be bifurcated on a number of spatial scalesin the manner of the fibers disposed on a Gecko foot. The implant canhave fibers attached by both ends in the polymeric substrate, thusdetermining loops, the radius of said loops of at least two lengthscales. The implant can have any combination of the above.

In describing the hierarchical structures of the present disclosure,“protuberance” refers to any higher structure on a macroscopicallyplanar surface and “depression” refers to any lower structure on amacroscopically planar surface. Generally, protuberances and depressionsare paired with respect to a specific spatial scale, and reporteddimensions thereof are made pair-wise. For example, when a protuberanceis reported to be 100 microns in height, that dimension is measured withrespect to a near-by depression. In engineering parlance, themeasurement is made peak to trough. Lateral measurements are typicallymade peak to peak or trough to trough, and are referred to as the pitch.

For the purposes of promoting an understanding of the principles of thedisclosure, reference will now be made to the embodiments illustrated inthe drawings and specific language will be used to describe the same. Itwill nevertheless be understood that no limitation of the scope of thedisclosure is thereby intended, such alterations and furthermodifications in the illustrated device, and such further applicationsof the principles of the disclosure as illustrated therein beingcontemplated as would normally occur to one skilled in the art to whichthe disclosure relates.

At least one embodiment of the present disclosure will be described andshown, and this application may show and/or describe other embodimentsof the present disclosure. It is understood that any reference to “thedisclosure” is a reference to an embodiment of a family of disclosures,with no single embodiment including an apparatus, process, orcomposition that must be included in all embodiments, unless otherwisestated.

Referring to FIG. 1A, an implantable prosthetic 100 of the presentdisclosure possesses a hierarchical surface comprised of a micro-scalestructure 102 with a plurality of protuberances 104 and depressions 106disposed in a geometric pattern on at least one surface of a substrate108, and a nano-scale structure 110 disposed on at least one surface ofthe micro-level structure 102. The nano-scale structure 110 is similarlycomprised of protuberances 112 and depressions 114. The implantableprosthetic 100 may include a first surface 109 and a second surface 111,as depicted in FIG. 1B.

The micro-scale protuberances 104 should be high enough so that a waterdrop does not touch the micro-scale depressions between adjacentprotuberances 104. In the embodiment of FIG. 1A, the micro-scaleprotuberances 104 may comprise a height H of between about 1 to about100 microns and a diameter D of between about 1 to about 50 microns,wherein the fraction of the surface area of the substrate 108 covered bythe protuberances 104 may range from between about 0.1 to about 0.9. Thenano-scale protuberances 112 may comprise a height h of between 1nanometer to about 1 micron and a diameter d of between 1 nanometer toabout 0.5 microns, wherein the fraction of the surface area of thesubstrate 108 covered by the protuberances 112 may range from betweenabout 0.1 to about 0.9. The nano-scale structure 110 may be disposedprimarily on the micro-scale protuberances 104, or alternativelyprimarily on the micro-scale depressions 106, or primarily uniformlyacross micro-scale structure 110.

The pitch P between adjacent micro-scale protuberances 104 ordepressions 106 may range from between about 1 and about 500 microns.The pitch p between adjacent nano-scale protuberances 112 or depressions114 may range from between 1 nanometer and about 10 microns.

The arrangement of hierarchical structures may be geometric ordescribable generally with a mathematical equation, as provided above.Alternatively, the hierarchical structures may be randomly disposed,possibly with varying pitch, which is more typical of naturalstructures. The arrangement of hierarchical structure can generally bedescribed by a fractal dimension, F. A fractal dimension is astatistical quantity that gives an indication of how completely acollection of structures appears to fill space, in the present case aplane, as one examines that structure on a multiplicity of spatialscales.

Specifying a fractal dimension, which is statistical in nature, does notnecessarily indicate that the hierarchical structure is well defined bya mathematical equation. Generally, a random arrangement of structureswithin a specific scale possesses a higher fractal dimension than one inwhich the structure is mathematically described at all points on asurface. Thus, a random structure may possess an advantage in the aspectthat a synthetic structure of the present disclosure has greater utilitywhen interacting with a natural surface such as tissue. A higher fractaldimension within a specific spatial scale may be achieved by applying toa substrate multiple pitch arrangements. The protuberances anddepressions may be locally scaled with respect to the local pitch.Accordingly, the pitch may vary within a scale structure. In thepractical realization of higher fractal dimension structures, thevariation of the pitch may be describable by a mathematical equation,for example, a sinusoidal variation of pitch, which would have utilityin mimicking natural surfaces.

Generally, structures can be described as sharp-edged or rounded, andthis feature is not typically captured by a fractal dimension. On theother hand, a Fourier decomposition of such structures would provide afractal-like dimension. For example, a sharp-edged structure wouldrequire a greater number of sinusoidal waveforms to describe such astructure in superposition. This corner roundness can be characterizedby a radius (R,r), and generally may be different in a direction xrelative to an orthogonal direction y in the plane of the implant.

Another structural aspect not addressed by the above descriptiveparameters is the degree of communication between structures. Bycommunication, it is meant that a structure, such as a protuberance or adepression, has a spatial extent greater than the pitch. For example, avalley surrounding a protuberance may be connected to another valleysurrounding another protuberance, thus the depressions are said to becommunicating whereas the protuberances are not. The degree ofcommunication or connectedness c or C (nano-scale or micro-scale,respectively) can be quantified by the ratio of the spatial extent inone direction, for example Dx, and the pitch in an orthogonal direction,for example Py. Accordingly, Cx=Dx/Py and cx=dx/py. Furthermore, thecommunication can vary across the surface of the substrate. Thecommunication may range from 1 to about 1000, more particularly thecommunication may extend over the entire surface of the substrate.

Referring to FIGS. 2a-c , in FIG. 2a a concentric circular structure 200is comprised of a first protuberance 202, a second protuberance 204 afirst valley 206 and a second valley 208 and is characterized by Dx, Dy,Px, Py. Note for non-varying pitch, the pitch is the same whethermeasured peak to peak 210 or trough to trough 212. Due to the circularstructure, Dx=Dy, Px=Py and D=P, which gives Cx=Cy=1. Now referring toFIG. 2b , wherein the structure is elliptical 230. In this instanceDx<Dy and Px<Py. Let 4Dx=Dy, 4Px=Py, and Dx=Px, then Cx=0.25 Nowreferring to FIG. 2c , wherein the structure is more elliptical 240. Inthis instance Dx<Dy and Px<Py. Let 100Dx=Dy, 100Px=Py, and Dy=Py, thenCx=1/100=0.01

In the limit where the valleys become parallel the communication Cx→0.Accordingly, structures of low communication can be constructed for bothdepressions and protuberances where reference to a flat, non-texturedlevel is made. For example, a texture may be impressed into a flatplanar surface wherein some of these textures are protuberances andother textures are depressions, separated by regions of flat planarsurface. Structures can be created wherein the depressions possess ahigh communication ratio and the protuberances possess a lowcommunication ratio, and conversely.

These structures are constructed with the purpose of creating Wenzel andCassie states, on a multiplicity of scales, when the prosthetic of thepresent disclosure is initially implanted and at a long period afterimplantation.

It is known in the art that the transition to the Wenzel state can bediscouraged by the use of sharp cornered features in the plane of thesurface. However, the occurrence of sharp cornered structures in naturalstructures, such as rose petals, is less common. Natural structures tendto possess rounded surface features, especially radiused or filletedcorners. In nature, resistance to conversion to a Wenzel state seems toinvolve the creation of involute rounded structures rather than sharpedges. By involute it is meant concavity oriented in a line notorthogonal to the substrate surface. Such structures are difficult tocreate by an etching or casting method, but can readily be created by anembossing method that entails folding of a structure. Similarly, theWenzel state can be discouraged by the use of curving communicationsbetween structures as opposed to straight line communication. In mostcases, higher hydrophobicity equates with lower propensity for a Wenzeltransition.

Alternatively, a prosthetic may be comprised of a substrate onto whichis deposited a first functional component with a discrete geometricstructure and a second functional component with a second discretegeometric structure.

One of the functional components may be hydrophobic, and may contain afluorine-containing moiety which associates with gas phase oxygen toalternatively associates with lipo-substances. The second functionalcomponent may be hydrophilic, and when implanted readily associates withwater. Upon implantation, the two functional components set up domainsof hydrophobic constituents derived from the implant environment anddomains of hydrophilic constituents derived from the implantenvironment. The structure is selected such that the implant derivedhydrophobic constituents bead or possess high surface tensionjuxtaposing the regions of implant derived hydrophilic constituents. Thedegree to which the implant derived constituents fill the geometry ofthe surface determines whether a Cassie or wettable Cassie state existslocally.

Wettable here means both the spread of aqueous components across theimplant surface and the spread of lipophilic components across theimplant surface. Thus, depending on the time and conditions surroundingthe implant, either the aqueous or lipo fractions may be relatively morespreading. Therefore, the implant surface may be simultaneously adhesiveto hydrophobic substances and repulsive to hydrophilic substances, orvice versa, and this condition may be designed to change with time. Forexample, the relative strengths of adhesivity and repulsivity may changewith time, or the condition of adhesivity/repulsivity may switch withrespect to hydrophilic or hydrophobic constituents.

Super hydrophobic surfaces relying solely on surface structure willeventually saturate with water as the gas phase entrapped on the surfacedissolves into the body and by the accumulation of amphilic substancedin biologic fluids. This saturation can be delayed or prevented by theuse of moieties that retain gas phase molecules, for example fluorinewith an affinity for gaseous oxygen. Alternatively, lipophilic regionscan be dispersed across the surface in parallel with surface morphologyto encourage accumulation of lipo-substances to the exclusion of wettingby water. Thus, such stable surfaces would continue to resist shearforces.

The hydrophobicity of a surface is enhanced by the placement of exteriorcorners around depressions. In some embodiments, this is achieved by thecreation of additional pairs of adjacent depression walls that projectinto and are joined at the interior of the depression. In someembodiments this is achieved by designing an ordered array ofdepressions of a first hierarchy (examples: triangular, rectangular,pentagonal, or hexagonal shapes, regular or irregular; and furtherpolygonal shapes defined generally by straight line segments). A secondfeature of smaller size and different hierarchical order is thensuperimposed on the depression wall of the first pattern. The methodemployed in creating such a structure may involve embossing ananostructure and then embossing a microstructure.

Alternatively, the substrate may be hydrophobic. Hydrophobic substancessuitable for implantation include polyesters made from aliphatic oraromatic dicarboxylic acids and aliphatic and/or aromatic diols, e.g.:polyesters synthesized from aliphatic dialcohols having 2 to 18 carbonatoms, e.g., propanediol, butanediol, hexanediol, and dicarboxylic acidshaving 3 to 18 carbon atoms, such as adipic acid and decanedicarboxylicacid; polyesters synthesized from bisphenol A and the above mentioneddicarboxylic acids having 3 to 18 carbon atoms; and polyesterssynthesized from terephthalic acid, aliphatic dialcohols having 2 to 18carbon atoms, and dicarboxylic acids having from 3 to 18 carbon atoms.

The polyesters may optionally be terminated by long-chain monoalcoholshaving 4 to 24 carbon atoms, such as 2-ethyl hexanol or octadecanol.Furthermore, the polyesters may be terminated by long-chainmonocarboxylic acids having 4 to 24 carbon atoms, such as stearic acid.In most cases, hydrophobicity is reduced by the presence of polarpendant groups, such as hydroxyls.

Alternatively, polymers containing urethane (carbamate) or urea links orcombinations of these can be made hydrophobic by varying the number ofthese links relative to the molecular weight of the amorphous phasebackbone, as well as varying the hydrophobicity of the backbone.Typically, such polymers are formed by combining diisocyanates withalcohols and/or amines. For example, combining toluene diisocyanate witha diol and a diamine under polymerizing conditions provides apolyurethane/polyurea composition having both urethane linkages and urealinkages. Such materials are typically prepared from the reaction of adiisocyanate and a polymer having a reactive portion (diol, diamine orhydroxyl and amine), and optionally, a chain extender.

Suitable diisocyanates include both aromatic and aliphatic diisocyanatessuch as toluene diisocyanate, 4,4′-diphenylmethane diisocyanate,3,3′-dimethyl-4,4′-biphenyl diisocyanate, naphthalene diisocyanate andparaphenylene diisocyanate. Suitable aliphatic diisocyanates include,for example, 1,6-hexamethylene diisocyanate (HDI),trimethylhexamethylene diisocyanate (TMDI), trans-1,4-cyclohexanediisocyanate (CHDI), 1,4-cyclohexane bis(methylene isocyanate) (BDI),1,3-cyclohexane bis(methylene isocyanate), isophorone diisocyanate(IPDI) and 4,4′-methylenebis(cyclohexyl isocyanate).

The alcoholic or amine containing polymer can be a diol, a diamine or acombination thereof. The diol can be a poly(alkylene)diol, apolyester-based diol, or a polycarbonate diol. As used herein, the term“poly(alkylene)diol” refers to polymers of alkylene glycols such aspoly(ethylene)diol, poly(propylene)diol and polytetramethylene etherdiol. The term “polyester-based diol” refers to a polymer such asethylene, 1,3-propylene, 1,2-propylene, 1,4-butylene,2,2-dimethyl-1,3-propylene, and the like. One of skill in the art willalso understand that the diester portion of the polymer can also vary.For example, the present disclosure also contemplates the use ofsuccinic acid esters, glutaric acid esters and the like.

Useful polymers for use in construction of the present disclosureinclude, for example, hydrophobic monomers olefins, cyclooletins,fluoroolefins, fluorochloroolefins, vinyl aromatics, diolefins such asbutadiene, isoprene and chlorobutadiene, and different monoethylenicallyunsaturated monomers that contain at least one alkyl group.

Suitable polyalkylene backbones for polymer construction include olefinssuch as ethylene, propylene, n-butene, isobutene, n-hexene, n-octene,isooctene, n-decene and isotridecene.

Hydrophobic monomers may be further synthesized by the addition offluorine, for example, fluorinate polyalkylene polymers such asfluorolefin, fluorochloroolefins such as vinylidene fluride,chlorotriluoroethylene and tetrafluoroethylene.

These polymeric constituents may be linked together in self-organizingnetworks or in chain-extended networks, crosslinked or not, using ureaor urethane links. Such links are typically formed using low molecularweight diisocyanates, but higher functional isocyanates are also usefulin achieving the polymeric networks of the present disclosure.

Bioabsorbable links may also be incorporated into the polymer network.Functional ends on the hierarchical structures of the present disclosuremay be capped with bioactive moieties, for example, boswellic acid orhyaluronate.

The polymers of the present disclosure may be combined withbiofunctional substances. In particular, implants with a texture-inducedmigration resistance may be clinically augmented by addition of abacteriocidal group. Examples of bacteriocides include silversulfadiazine, chlorhexidine, glutaraldehyde, peracetic acid, sodiumhypochlorite, phenols, phenolic compounds, iodophor compounds,quaternary ammonium compounds, and chlorine compounds, in addition toclinically useful antibiotics.

In construction of a hierarchical morphology and also depositing ahydrophobic/hydrophilic structure, a cast of a suitable hierarchicalstructure may be used. For example, a crystalline structure or a cast ofa biologic surface known to have such structure. Suitable biologicalsurfaces include petals, for example red rose petals, and leaves, forexample lotus leaves. The cast can be made with a hydrophobic substancethat can be latter removed from a surface formed thereon. A suitablecasting medium might be methylcellulose.

The methods of manufacture of an implantable prosthetic of the presentdisclosure include lithography, casting, extrusion/embossing, and any ofseveral methods for transferring a texture to a surface. A preferredmethod is embossing. Referring now to FIG. 3, a polymeric substance isheated to a molten state and passed through dual rollers, at least oneof which contains a negative image of the desired embossed structure. Inthe instance of FIG. 3, a nano-scale texture 302 is embossed on a formedplanar sheet 300, as depicted in FIG. 3a . As depicted in FIG. 3b ,formed sheet 300 is heated to a malleable but not fluid state and passedthrough dual rollers 304 possessing a micro-scale texture 306 whichimpresses an inverse image. The micro-scale texture 306 is largerelative to the nano-scale texture 302, thus the impression of themicro-scale texture 306 folds the nano-scale texture 302, makingpossible involute structures 308. The method depicted in FIG. 3 may beimproved by heating from the non-textured side, so that the texturedside is cooler and the nano-scale texture is less likely to be deformedby impressing the micro-scale texture over the nano-scale texture.

Surface textures from fluorinated polyalkyelene polymers of specificmolecular weight may be constructed by chain extension oftetrafluoroethylene using diisocyanates in ratio that provides separatepolymers chains of a desired length. This solution can then be suspendedin water and precipitated on a casting surface of methylcellulose. Oncethe cast surface is coated with hydrophobic polymeric chains, the watercan be removed and the surface dried, and a self-assembling prepolymerof triol of ethylene oxide/propylene oxide endcapped with isocyante canbe polymerized on the surface, which then incorporates thefluoro-polymer in the polymerized volume. Subsequently themethylcellulose mold is dissolved with ether to provide a surface ofhierarchical structure.

Other methods of making a structured surface to be used as a templateinvolve multi-phase deposition, chemical or photo etching, the use ofmetal powders, fibers and the like deposited on a surface in a specificareal density. Furthermore, the polymeric structure itself may becomprised of alternating hydrophobic and hydrophilic units, the densityand distribution of these units being selected by appropriate choice ofmolecular weight of the monomeric units and fraction ratios. Thus, asurface texture may comprise both spatially varying materials withdifferent hydrophobicity and topological textures.

In particular, a multiplicity of structural and/orhydrophilic-hydrophobic states may be selected not only to span at leastone order of magnitude in size or distribution, but these scales may berelated in a self-similar way and may possess a fractal dimension.Particular fractal dimensions may be useful in their repulsive effect,and others may be useful in their attractive effect.

Other approaches may include absorbable polymers designed to transitionfrom a Cassie state to a wettable Cassie state and finally to a Wenzelstate. For example, grooves in an absorbable substrate of at least twoscales are made which are non-communicating. As the substrate absorbs,the individual grooves begin to form communicating interfaces whichtransition into a wettable Cassie state. As the microstructure breaksdown further, the surface becomes increasingly proximal to surroundingwater, and eventually enters a Wenzel state. For example, a Cassie toWenzel state can be achieved when the ratio of groove height to groovewidth decreases.

Additionally, a desired surface may be coated with a water-solublelipophilic substance which provides the desired phase separatecomponents between aqueous biologic fluid and the solubilized coating,such that the solubilized coating beads on the implant surfacesubsequent to implantation. Alternatively, the coating may be partiallybioabsorbable, which fractionates into the nano or micro particles thatthen associate with the implant surface according to its surfacestructure to form the desired Cassie state in vivo.

A desired Cassie state of the present disclosure may be achieved byforming a foam with a multiplicity of porous dimensions. The desireddistribution of porous dimensions may be realized as a consequence oftemperature, pressure or changes in viscosity as the prepolymerspolymerizes. Alternatively, the prepolymers may be crosslinked in thepresence of nucleating particles of different size. In particular, anisocyanate prepolymer may be used which liberates gas phase carbondioxide when mixed with water. The reaction may precipitate out of watersuspension as it polymerizes forming a layer, or may polymerize entirelyin its volume, after which the water is removed. Accordingly, thedesired Cassie state of the present disclosure may be achieved not onlyon a surface but also throughout a volume. These three-dimensionalCassie volumes are of particular use in tissue scaffold applications.Such scaffolds may be bioabsorbable or permanent.

The composition of the present disclosure may be free of substantiallyfree of any optional or selected ingredients described herein.

All references to singular characteristics or limitations of the presentdisclosure shall include the corresponding plural characteristic orlimitation, and vice versa, unless otherwise specified or clearlyimplied to the contrary by the context in which the reference is made.

All combinations of method or process steps as used herein can beperformed in any order, unless otherwise specified or clearly implied tothe contrary by the context in which the referenced combination is made.

As used herein, the term “about” should be construed to refer to both ofthe numbers specified in any range. Any reference to a range should beconsidered as providing support for any subset within that range.

Examples are provided to illustrate some embodiments of the embodimentsof the present disclosure but should not be interpreted as anylimitation thereon. Other embodiments within the scope of the claimsherein will be apparent to one skilled in the art from the considerationof the specification or practice of the embodiments herein. It isintended that the specification, together with the example, beconsidered to be exemplary only, with the scope and spirit of thedisclosure being indicated by the claims which follow the example.

Examples

In these examples the following variables will be used to describe thesurface texture. An upper case variable denotes that variable measuredon a large scale, and a lower case variable denotes that variablemeasured on a smaller scale. By extrapolation, structures comprisingmore than two texture scales are anticipated. Height (H) is measured onthe structure of largest connectedness (C) value, whether it be apositive (protuberance) or negative (valley) structure. The variables xand y denote orthogonal coordinates in the plane of the surface of thedevice. A variable associated with another variable in parenthesesdenotes the first variable is a function of a second variable, forexample F(x) denotes the fractal dimension varies as a function of thespatial dimension x.

H,h=height, measured orthogonal to the plane of the surface, peak totrough

D,d=diameter, measured in the plane of the surface, 2×lateral peak totrough, x and y values

P,p=pitch, measured in the plane of the surface, peak to peak, x and yvalue

F,f=fractal dimension

R,r=corner radius, x and y values

C,c=connectedness

Example 1

A planar implant comprising a tissue adhesive surface on one side and atissue anti-adhesive surface on the other side. The implant may possessholes that pass through the planar implant allowing for tissue to growthrough the implant. In this aspect, the present example is novel infunctionality in that the tissue through-growth does not promote tissueadhesion to adjacent tissue surfaces since it is well vascularizedtissue which is distinct from scar tissue which is not well-vascularizedand tissue adhesive.

Accordingly, the above implant may possess a petal effect on the tissueadhesive side and a lotus effect on the tissue anti-adhesive side. Theanti-adhesive side would be super hydrophobic, possessing a surfacetexture with spatially hierarchical roughness, wherein the contact angleat every scale of surface roughness is substantially of Cassie type. Thetissue adhesive side would be super hydrophobic, possessing a surfacetexture with spatially hierarchical roughness, wherein the contact angleat some scales of surface roughness is substantially of Cassie type andat other scales of roughness is of Wenzel type. In particular, thosescales of surface roughness that on average are spatially larger arepredominately of Wenzel type. Those scales of surface roughness that areon average spatially smaller are predominately of Cassie type.

Variations on the present example characteristically possess a largecontact hysteresis on the tissue adhesive side and a relatively smallercontact hysteresis on the tissue anti-adhesive side. Further variationsof the present example characteristically retain their respectivecontact hysteresis on each side of the implant due to a contactequilibrium that is established by the combination of hydrophobicityhierarchically scaled structures and surface roughness hierarchicallyscaled structures.

Example 2

A surgical barrier comprised of a nonporous layer which on one sidepossesses a high contact hysteresis angle and on the other sidepossesses a low contact hysteresis angle wherein first high contacthysteresis angle is sufficiently large to generate a rapid andreversible adhesion to tissue. The rapidity of adhesivity being largelydetermined by the energy required to form a solid/liquid interface andthe ease of reversibility being largely determined by the energyrequired to dis-associate a solid/liquid interface.

Example 3

A tissue scaffold for soft tissue repair, wherein all surfaces areadhesive. The implant may be substantially porous to allow tissueincorporation and to direct neovascularization of the implant. Theimplant may be bioabsorbable. Said surfaces characteristically possess ahigh contact angle hysteresis. The contact angle hysteresis may be smallon exterior surfaces as compared to internal porous surfaces to promotetissue incorporation without promoting excessive adjacent tissueadhesions. Alternatively, the external surface may possess a contactangle hysteresis that is greater than the internal contact anglehysteresis. Such an implant might be used in a context where greateradhesivity between adjacent tissue layers is desirable in a soft tissuerepair.

Example 4

An absorbable soft tissue repair implant wherein the immediate surfacehas a desired texture, and as this layer is solubilized by the body,successive layers are revealed with varying surface textures. Forexample, an implant of the present example wherein the contact anglehysteresis reduces as the implant absorbs. Alternatively, an implant ofthe present disclosure wherein the contact angle hysteresis increases asthe implant absorbs. The former being useful in a surgical applicationwhere native tissue healing is aggressive, either by virtue of a robustphysiology or due to the position of the implant within the body. Thelater, being useful in a surgical application where native tissuehealing is weak, either by virtue of a genetic or pathological conditionwherein certain types of collagen are inadequately synthesized or due tothe position of the implant within the body.

Alternatively, variations of the present example may possess variablecontact angle hysteresis either spatial or at depth within theabsorbable implant. For example, both the value of the contact anglehysteresis may vary as well as the thickness or mass of adjacent layersof singular contact angle hysteresis.

Example 5

Implants of Example 1-4 wherein at least part of the implant iscomprised of fluoro-hydrocarbons. For example, polyurethane synthesizedwith a fluoro diisocyanate. Alternatively, polyurethane synthesized witha polyol wherein at least some of the carbons are replaced by fluorine.

Example 6

Implants of Examples 5 wherein oxygen is adsorbed to the implant priorto implantation, thereby locking to the implant surface a gaseous phasecomprised substantially of oxygen. This oxygen could be released over aperiod of time in vivo, thus further promoting tissue infiltration ofthe implant. Additionally, the surface oxygen may impede or kill varioustypes of bacterial colonization. Lastly, said attached oxygen couldbenefit a soft tissue repair which is characteristically avascular ortemporarily devoid of systemically supplied oxygen.

Example 7: Implant where the Surface Texture Satisfies D not Equal to P

A regular array of protuberances or valleys with height H, wherein thediameter D of the protuberances or valleys is different from the spacingP between such structures.

Example 8: Implant where the Surface Texture Possesses SinusoidallyVarying Height

A regular array of approximately conical protuberances or valleys withheight H(x,y)=A sin(x,y), where sin(x,y) can denote any ofsin(x)+sin(y), sin(x)sin(y), sin(xy), sin(x+y).

Example 9: Implant where the Surface Texture Satisfies D(x) andP=Constant

A regular array of approximately conical protuberances or valleys withvarying diameter D(x,y)=A sin(xy) and constant distance betweenprotuberances or valleys P.

Example 10 Implant where the Surface Texture Satisfies P(x) andD=Constant

A regular array of approximately conical protuberances or valleys withvarying spacing P(x,y)=A sin(xy) and constant protuberance or valleydiameter D.

Example 11: Implant where the Surface Texture is a Koch Snowflake

The surface constructed by starting with an approximately conicalprotuberance or valley, then recursively altering each protuberance orvalley as follows:

1. Draw two line segments, running peak to trough, intersecting the peakorthogonally (see FIG. 7A);2. divide each line segment into three segments of equal length;3. Place a conical protuberance or valley centered on each of the middlesegments of step 2 (see FIG. 7B);4. Repeat steps 1-3 on the protuberances or valleys of step 3. (See FIG.7C). The resulting shape is shown in cross section in FIG. 7D withfractal dimension F=1.26.

Example 12: Implant where the Surface Texture is a Sierpinski Gasket

An algorithm for obtaining arbitrarily close approximations to theSierpinski triangle is as follows

1. Tile the implant surface with maximal sized triangles;2. Shrink the triangle to ½ height and ½ width, make three copies, andposition the three shrunken triangles so that each triangle touches thetwo other triangles at a corner;3. Note the emergence of the central hole (FIG. 4);4. Apply step 2 to the largest remaining triangles.Replace the triangles with either tetrahedrons or cones, either positiveor negative (FIG. 4). The resulting structure has fractal dimensionF=1.59.

Example 13: Implant where the Surface Texture is an Apollonian Gasket

Tile the implant surface with three circles C₁, C₂ and C₃, each one ofwhich is tangent to the other two (these three circles can be any size,as long as they have common tangents). Apollonius discovered that thereare two other non-intersecting circles, C₄ and C₅, which have theproperty that they are tangent to all three of the originalcircles—these are called Apollonian circles. Adding the two Apolloniancircles to the original three, we now have five circles (FIG. 5).

Take one of the two Apollonian circles—say C₄. It is tangent to C₁ andC₂, so the triplet of circles C₄, C₁ and C₂ has its own two Apolloniancircles. We already know one of these—it is C₃—but the other is a newcircle C₆.

In a similar way we can construct another new circle C₇ that is tangentto C₄, C₂ and C₃, and another circle C₈ from C₁, C₃ and C₁. This givesus 3 new circles. We can construct another three new circles from C₅,giving six new circles altogether. Together with the circles C₁ to C₅,this gives a total of 11 circles.

Continuing the construction stage by stage in this way, we can add2·3^(n) new circles at stage n, giving a total of 3^(n+1)+2 circlesafter n stages. In the limit, this set of circles is an Apolloniangasket.

The Apollonian gasket has a fractal dimension F=1.3057. The circles canbe replaced with positive or negative cones.

Example 14: Implant where the Surface Texture is a Diffusion LimitedAggregation

The implant surface was partitioned into an approximately circular gridof square cells. The cell at the center of the circle is the location ofthe seed point. Now pick a square on the perimeter of the grid and placea random function on that square. Randomly, advance the state of thefunction to one of the four adjacent squares. If this function leavesthe implant surface another seed point is started, chosen randomly atthe edge. When the function arrives at one of four squares adjacent tothe seed point, it stops there forming a cluster of two seed points,each releasing a new function. Continuing in this way builds anaggregate illustrated in FIG. 6. Now replace the linear trace witheither a protuberance or a valley, generally these structures areinscribed on a larger scale structure of conical protuberances orvalleys

Example 15: Implant where the Surface Texture Makes the ImplantHydrophobic to Reduce the Rate of Absorption

The disclosure relates to implantable, absorbable sheets which arehydrophilic, and possibly swell or even dissolve in situ, whereby theaddition of a hydrophobic structure reduces the rate of absorption orconformal change in situ. Accordingly, two scales of depressions,approximately cylindrical or conical are preferred. Referring to FIG. 9,a textured surface 900 interface with tissue 901 comprises first scaledepressions 902 and first scale protuberances 903 and second scaledepressions 904. Water layer 906 interacts only with ridges 908 formedby the first scale 902 and second scale 904 structures. Air 910 andlater lipids 912 surround the second scale features. Thus, the surfacearea presented to water is significantly reduced.

Example 16: Absorbable Hydrophobic Implantables Made Hydrophilic

Alternatively, the disclosure relates to physiologically absorbable,generally fibrogenic, hydrophobic materials that are made relativelyhydrophilic during a first interval by the addition of surface texture.Structures of this type resemble corals. Accordingly, two scales ofridges, with a high connectedness number and tortuosity are preferred.Referring to FIG. 10, a textured surface 1000 comprises first scaleridges 1002 and orthogonally arranged second scale ridges 1004. Waterlayer 1006 wicks 1008 first into small scale ridges 1004 which drains1010 into large scale ridges 1002. Eventually the entire implant surfaceis coated with a thin layer of water, which without the surface texturewould have been coated by protein.

Example 17: Absorbable Hydrophobic Implantables Made Hydrophilic toIncrease the Rate of Absorption

Alternatively, the disclosure relates to hydrophobic implantable sheetsthat do not absorb quickly in the body, which are made to absorb morequickly with the addition of a hydrophilic structure. Accordingly, twoheight scales of pillars are preferred. Referring to FIG. 11, a texturedsurface 1100 interacting with tissue 1001 comprises first scale pillars1102 and between these second scale pillars 1104. The first scalepillars form spaces 1106 which induce a capillary effect 1108, andactively draw water 1108 into the spaces 1106 as the implant materialdissolves into the water 1110. The second scale pillars 1104 formsmaller spaces 1112 that further drive water 1114 deeper into thesubstrate. Hence, the surface area in contact with water issignificantly increased.

Example 18: Implantables with at Least One Side Immediately TissueAdhesive

Surgical barrier implants block tissue adhesions between adjacent layersof tissue. Due to their anti-adhesive functionality, they tend tomigrate after implantation requiring localization by suture or staple.These localization points then become foci for tissue adhesion. Acombination of Wenzel and Cassie states creates a Cassie wettingcondition characterized by a large contact angle hysteresis.Accordingly, these textures are not energetically favored to slideacross a surface.

Referring to FIG. 8, a Cassie wetting texture 800 interacting withtissue 801 is comprised of first scale protuberances 802 and secondscale ridges 804 oriented axially with protuberances 802 and distributedcircumferentially. The ridges 804 enter the Wenzel state when placed ontissue. The Wenzel state is prevented from moving in the plane of theimplant by the adjacent Cassie states created by the protuberances 802.

Efficacy Studies Example 19

The following are efficacy studies carried out on petal structures ofthe present disclosure, in particular regarding shear forces.

In a first study, we made casts directly from organic red T-rose petals.Direct casts reproduce the surface texture as a negative of the originalpattern. Positive casts were made by creating a negative mold and thencasting a positive from the negative mold.

A number of casting materials were tested, including hot wax, wax intoluene, nail polish, hot glue, cyanoacrylate, plaster, polylactic acid(PLA 708, Boehringer-Ingelheim), silicone rubber, and pyroxylin. Onlythe latter three were successful, the silicone rubber being the mostdependable in terms of reproducing the petal surface.

A limited shear test was performed with a small quantity of positiveimage PLA sheets. The procedure consisted of forming a negativepyroxylin cast, pouring PLA acetone solution over the negative cast, anddissolving away with ethanol the pyroxylin portion. Later we usedsilicone to create the negative mold, with similar results.

Mechanical localization (shear stress) was assessed. Cutlets of bovine“steak” were purchased and sliced into 3 cm cubes and affixed to alocalized platform. The meat was kept well hydrated with physiologicsaline solution at 22° C. Test articles were cut to 1×1 cm squares andmounted on discs to which was attached the filament through which forcewould be applied to the test article. Shear was measured by placing thestrip on the 3 cm cube of meat and pulling parallel to the surface.Thus, these measurements yield a force per unit area (1 cm²). Inpreliminary testing, there was no difference in shear force immediatelyvs 1 hour later. Thus, there was no observable saturation effect, andshears were not measured at different time intervals.

Two wetting scenarios were tested. In one scenario, the tissue surfacewas kept moist to replicate normal surgical conditions (wet to touch),but no standing water. In another, the tissue and test articles wereimmersed in water. The buoyancy of the disc support was minimal.However, a rather more complicate pulley system was employed for testingin water, which in the worst case should result in lower shear forcessince the resistance to shear would be communicated less efficiently tothe sensor, and thus the force measured lower.

In all measurements, clear outliers were discarded, and when possible,the run was repeated with additional test articles.

An Instron Mini 55 was used to record force and the crosshead speed was0.1 cm/sec. The load cell limit was 200 g with an accuracy of +/−0.1 g.

Shear Force Measurement

All measurement rounded to nearest gram. All measurements were done witha 0.5 gram disc. All measurements were done with fresh casts to avoidtexture filling, but variations in thickness could contribute tovariable changes. Whenever possible, experiments comparing differentattributes were done with casting made at the same time to avoid changesin casting solution or ambient conditions. Results are summarized inTables 1-4.

TABLE 1 Negative Vs Positive Shear (submerged in water) Texture (gramsforce) Negative of organic rose (PLA) N = 3 105 +/− 36 Positive oforganic rose (PLA) N = 3  37 +/− 12

TABLE 2 Pyroxylin Vs PLA Casts Shear (submerged in water) Texture(negative) (grams force) Pyloxyrin of organic rose (N = 5)  79 +/− 32PLA of organic rose (N = 5) 107 +/− 35

TABLE 3 Kinetic Vs Static Shear Force - Tissue submersed in water Shear(submerged in water) Texture (negative, PLA, organic rose) (grams force)kinetic (N = 10) 101 +/− 22 Static (N = 10) 119 +/− 35

TABLE 4 Wet tissue Texture (negative, PLA, organic rose) Shear (wet)(grams force) kinetic (N = 10) 27 +/− 11 Static (N = 10) 32 +/− 9 

Shear Tests of Manmade Patterns

All measurement rounded to nearest gram. All measurements were done witha 0.5 gram disc. All measurements were done with fresh casts to avoidtexture filling. The following are tests conducted using silicone moldscast directly from organic rose and from manmade designs. The casts fromthe waffle design were comprised of 10- and 20-micron square depressionsseparated by 5-micron walls. The casts from the pillar design werecomprised of 5-micron diameter and 15-micron tall cylinders spaced intwo-dimensions on 20-micron centers. The casts from the Hrose designwere 10-micron tall pyramids with 15-micron square bases spaced in twodimensions on 20-micron centers. The above are the positive states, andthe negative states would be the spatial inverse. For example, pillarswould become cylindrical depressions.

The Hrose patterns were made by a lithography process on silicon wafers.We made two silicon molds (run 1 and run 2) from which were madesilicone molds. Results are summarized in Table 5.

TABLE 5 Negative Vs Positive Shear (submerged in water) Texture (gramsforce) 10 micron waffle (PLA) N = 3 Not measurable 20 micron waffle(PLA) N = 3 5 +/− 5 Pillar (PLA) N = 3 5 +/− 5 Hrose positive run 1(PLA) N = 3 61 +/− 18 Positive from silicone organic 117 +/− 15  rose(PLA) N = 3 Hrose positive run 2 (PLA) N = 3 56 +/− 21

The effect of using different viscosity solutions of PLA and apolyurethane (AP1959) as casting materials was studied regarding shearforce. High viscosity was 1000 cps and low viscosity was 10 cps. Resultsare summarized in Table 6:

TABLE 6 Texture Moist meat (grams force) High Viscosity positive Hroserun 2 (PLA)  58 +/− 14 N = 3 High Viscosity positive Hrose run 2(AP1959) 33 +/− 9 N = 3 Low Viscosity positive Hrose run 2 (PLA)  84 +/−29 N = 3 Low viscosity positive Hrose run 2 (AP1959)  47 +/− 14 N = 3Low viscosity positive Hrose run 2 (PLA) + 120 +/− 11 methylcelluloseLow viscosity positive Hrose run 2 (AP1959) + 127 +/− 16 methylcellulose

The Hrose patterns impregnated with methylcellulose provided the highestshear forces. The methylcellulose acts as an initiator for the formationof a hydrophobic Wenzel state.

In a last study, a nickel coated silicon mold was made with 52 different1 cm×1 cm surface patterns. The shear forces for these patterns weremeasured. Initial test of the adhesivity of PLA cast patterns on porkchop were disappointing. It was concluded the patterns were too fine toprovide adhesion to muscle tissue. Turning to the adhesivity onpericardium, which is very flat, it was decided to adopt a morepericardia-like surface. Egg white (albumin) was separated and slowlymicrowaved to provide a smooth protein surface.

Adhesivity was measured by attaching suture to an individual PLA casttextured square. The square was weighted with a 1-gram disc and placedon the albumin sheet. The suture was directed horizontally to a pulleyand passed over the pulley and directed vertically. At the terminus ofthe suture a 25 g weight was attached. The weight was placed on adigital scale. A platform comprising the test sample and pulley wasarranged on a lift that could be mechanically raised vertically. Thus,when the platform was raised, weight is transferred to the specimen, andthe resulting reduction of weight on the scale was recorded at theminimum.

The adhesivity was measured 10 times, and the mean and standarddeviation recorded. The pattern descriptions and adhesivity measurementsare described in Table 7.

TABLE 7 Pattern Descriptions (dimensions in microns). Pattern DimensionsAdhesivity Triangles Pattern 1, 6 20 × 20 × 20 0 2.3 +/− 0.7 Pattern 2,7 20 × 40 × 40 2.1 +/− 0.5 9.8 +/− 1.2 Pattern 3, 8 20 × 80 × 80 0 5.3+/− 0.6 Lines 11, 13 30 wide, 30 space 10.3 +/− 0.9 15.2 +/− 1.1 12, 4330 wide, 10 space 2.4 +/− 0.8 6.1 +/− 0.8 27, 34 30 wide, 60 space 2.2+/− 0.6 5.6 +/− 0.6 15, 50 5 wide, 5 space 0 11.2 +/− 1.2 16, 51 5 wide,10 space 5.6 +/− 1.1 17.2 +/− 2.4 17, 52 5 wide, 20 space 6.1 +/− 1.01.1 +/− 0.3 23, 41 10 wide, 10 space 4.7 +/− 0.7 2.4 +/− 0.7 24, 47 10wide, 20 space 2.3 +/− 0.6 5.5 +/− 0.9 25, 48 10 wide, 40 space 2.7 +/−0.7 0 Columns  5, 32 10 wide ¼ circle, 10 inner 5.3 +/− 0.8 8.2 +/− 1.3radius, jagged 19, 31 10 wide, ¼ circle, 10 inner 5.8 +/− 0.9 8.9 +/−1.2 radius 29, 49 10 wide, ½ circle, 10 inner 7.7 +/− 1.2 6.5 +/− 0.9radius (skew array) 30, 35 10 wide, ½ circle, 10 inner 3.1 +/− 0.9 8.9+/− 0.7 radius (rectangular array) Jagged Lines  4, 9, 10 10 wide, 1side 0 12.2 +/− 1.4 1.9 +/− 0.6 jagged, 10 space 33, 40 10 wide, jagged,20 space 11.2 +/− 1.0 3.1 +/− 0.7 18, 20 30 wide, jagged, 30 space 2.4+/− 0.7 8.3 +/− 1.1 26, 28 30 wide, jagged, 10 space 10.8 +/− 1.3 15.7+/− 2.1 Rectangles 36, 42 120 × 30 rectangles, long 2.4 +/− 1.1 6.4 +/−0.8 side jagged 37 120 × 30 rectangle, short side jagged 38 60 × 30rectangle, short side jagged, 10 space 39 30 × 30 rectangle, 1 sidejagged, 10 space 44 120 × 30 rectangle, 10 space 45 60 × 30 rectangle,10 space 46 30 × 30 rectangle, 10 space

Results

The textures can be categorized by straight line, curved segments,straight line with saw edge, rectangles with saw edge, grid of circles(positive), grid of circles (negative), grid of triangles, and/or gridof squares. Variability occurred in multiple casts from the same texturepattern. The main causes of variation were discovered to be remnant PLAin the mold, folded/deformed texture, and poor reproducibility on sawedged structures.

All adhesivity measured as grams/cm{circumflex over ( )}2. The firstvalue is the static shear force for the first listed pattern. The secondvalue is the static shear force for the second listed pattern. The thirdvalue is the static shear force for the third listed pattern.

What is claimed is:
 1. A medical device for contacting tissuecomprising: a substrate having a first side and an opposing second side;the first side having a first microstructured surface, the firstmicrostructured surface comprising a first surface texture and a secondsurface texture wherein the second surface texture is disposedhierarchically on the first surface texture, the first surface texturehaving a plurality of first microfeatures with a pitch between adjacentfirst microfeatures ranging from 1 micron to 500 microns, the secondsurface texture having a plurality of second microfeatures havingphysical dimensions smaller than the plurality of first microfeatures,and wherein the first microstructured surface is configured to generatean adhesion to tissue; the opposing second side having a secondmicrostructured surface, the second microstructured surface comprising athird surface texture configured to generate a superhydrophobic surface.2. The medical device of claim 1 wherein the plurality of firstmicrofeatures include a height ranging from 1 micron to 100 microns. 3.The medical device of claim 1 wherein at least two microfeatures of theplurality of second microfeatures are disposed on one of the firstmicrofeatures.
 4. The medical device of claim 1 wherein in an implantedstate the first side generates a tissue localization force and theopposing second side is resistant to tissue adhesion.
 5. The medicaldevice of claim 1 wherein the first side is capable of creating a shearforce exceeding 50 grams per square centimeter as tested by the moistmeat shear force test to translate the device relative to the tissue. 6.The medical device of claim 1 wherein the first side is configured togenerate a Cassie wettable state and the opposing second side isconfigured to generate a pure Cassie state.
 8. The medical device ofclaim 1, wherein the second microstructured surface further comprises afourth surface texture wherein the fourth surface texture is disposedhierarchically on the third surface texture, the third surface texturehaving a plurality of third microfeatures and the fourth surface texturehaving a plurality of fourth microfeatures wherein the plurality offourth microfeatures include physical dimensions smaller than theplurality of third microfeatures.
 9. The medical device of claim 1,wherein the substrate comprises a polylactic acid.
 10. The medicaldevice of claim 1, wherein the substrate comprisespolytetrafluoroethylene.
 11. The medical device of claim 1, wherein atleast a portion of the substrate is porous.
 12. The medical device ofclaim 1, wherein at least a portion of the plurality of firstmicrofeatures are in a triangular arrangement along the substrate. 13.The medical device of claim 1, wherein the medical device is configuredto be implanted into a host.
 14. The medical device of claim 13, whereinupon implantation, the first side is capable of forming a Wenzel-Cassiestate when in contact with tissue, and the opposing second side iscapable of forming a Cassie state that resists adhesion of a hostderived substance.
 15. The medical device of claim 13, wherein awater-based composition adheres to the first surface texture or secondsurface texture, and a lipid-based composition adheres to the firstsurface texture or second surface texture, provided that the water-basedand lipid-based compositions occupy different surface textures.
 16. Themedical device of claim 1, wherein the substrate is bioabsorbable andthe opposing second side has a slower absorbance rate than the firstside.
 17. A medical device for contacting tissue comprising: a substratehaving a first side and an opposing second side; the first side and theopposing second side having the same microstructured surface, themicrostructured surface comprising a first surface texture and a secondsurface texture wherein the second surface texture is disposedhierarchically on the first surface texture, the first surface texturehaving a plurality of first microfeatures with a pitch between adjacentfirst microfeatures ranging from 1 micron to 500 microns, the secondsurface texture having a plurality of second microfeatures havingphysical dimensions smaller than the plurality of first microfeatures,and wherein the first microstructured surface is capable of generatingan adhesion to tissue.
 18. The medical device of claim 17 wherein theplurality of first microfeatures include a height ranging from 1 micronto 100 microns.
 19. The medical device of claim 17 wherein at least oneof the plurality of first microfeatures includes disposed thereon atleast two microfeatures of the plurality of second microfeatures. 20.The medical device of claim 17 wherein the first surface texture andsecond surface texture cooperate such that a shear force exceeding 50grams per square centimeter as tested by the moist meat shear force testis required to translate the device relative to the contacting tissue.